DE3118588C2 - Verfahren zur Herstellung eines injizierbaren hochreinen Chondroitinpolysulfates, hiernach erhältliches Produkt und pharmazeutische Zusammensetzung - Google Patents
Verfahren zur Herstellung eines injizierbaren hochreinen Chondroitinpolysulfates, hiernach erhältliches Produkt und pharmazeutische ZusammensetzungInfo
- Publication number
- DE3118588C2 DE3118588C2 DE3118588A DE3118588A DE3118588C2 DE 3118588 C2 DE3118588 C2 DE 3118588C2 DE 3118588 A DE3118588 A DE 3118588A DE 3118588 A DE3118588 A DE 3118588A DE 3118588 C2 DE3118588 C2 DE 3118588C2
- Authority
- DE
- Germany
- Prior art keywords
- chondroitin
- methanol
- polysulphate
- polysulfate
- chondroitin polysulfate
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired
Links
- DLGJWSVWTWEWBJ-HGGSSLSASA-N chondroitin Chemical compound CC(O)=N[C@@H]1[C@H](O)O[C@H](CO)[C@H](O)[C@@H]1OC1[C@H](O)[C@H](O)C=C(C(O)=O)O1 DLGJWSVWTWEWBJ-HGGSSLSASA-N 0.000 title claims abstract description 82
- 229920002567 Chondroitin Polymers 0.000 title claims abstract description 81
- 238000000034 method Methods 0.000 title claims abstract description 39
- 239000008194 pharmaceutical composition Substances 0.000 title abstract description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims abstract description 168
- KFSLWBXXFJQRDL-UHFFFAOYSA-N Peracetic acid Chemical compound CC(=O)OO KFSLWBXXFJQRDL-UHFFFAOYSA-N 0.000 claims abstract description 32
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims abstract description 24
- 238000001556 precipitation Methods 0.000 claims abstract description 14
- 238000000108 ultra-filtration Methods 0.000 claims abstract description 13
- 150000001768 cations Chemical class 0.000 claims abstract description 6
- 238000004519 manufacturing process Methods 0.000 claims abstract description 5
- 150000003839 salts Chemical class 0.000 claims description 20
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 claims description 17
- 239000012528 membrane Substances 0.000 claims description 13
- 239000000126 substance Substances 0.000 claims description 13
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 10
- 229910001385 heavy metal Inorganic materials 0.000 claims description 10
- 239000002253 acid Substances 0.000 claims description 9
- 230000007717 exclusion Effects 0.000 claims description 9
- 238000005194 fractionation Methods 0.000 claims description 9
- 239000008139 complexing agent Substances 0.000 claims description 8
- 229910017052 cobalt Inorganic materials 0.000 claims description 5
- 239000010941 cobalt Substances 0.000 claims description 5
- GUTLYIVDDKVIGB-UHFFFAOYSA-N cobalt atom Chemical compound [Co] GUTLYIVDDKVIGB-UHFFFAOYSA-N 0.000 claims description 5
- 229910052742 iron Inorganic materials 0.000 claims description 5
- 230000001590 oxidative effect Effects 0.000 claims description 5
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 claims description 4
- 229960001484 edetic acid Drugs 0.000 claims description 4
- PWHULOQIROXLJO-UHFFFAOYSA-N Manganese Chemical compound [Mn] PWHULOQIROXLJO-UHFFFAOYSA-N 0.000 claims description 3
- 238000010306 acid treatment Methods 0.000 claims description 3
- 229910052748 manganese Inorganic materials 0.000 claims description 3
- 239000011572 manganese Substances 0.000 claims description 3
- 239000012429 reaction media Substances 0.000 claims description 3
- HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 claims description 3
- 235000010262 sodium metabisulphite Nutrition 0.000 claims description 3
- 150000002696 manganese Chemical class 0.000 claims 1
- 230000004048 modification Effects 0.000 claims 1
- 238000012986 modification Methods 0.000 claims 1
- 150000003681 vanadium Chemical class 0.000 claims 1
- 241000282472 Canis lupus familiaris Species 0.000 abstract description 5
- 241000282326 Felis catus Species 0.000 abstract description 4
- 238000011785 NMRI mouse Methods 0.000 abstract description 4
- 241000700157 Rattus norvegicus Species 0.000 abstract description 4
- 230000007059 acute toxicity Effects 0.000 abstract description 4
- 231100000403 acute toxicity Toxicity 0.000 abstract description 4
- 241000282414 Homo sapiens Species 0.000 abstract description 3
- 239000003814 drug Substances 0.000 abstract description 3
- 239000000243 solution Substances 0.000 description 38
- FAPWRFPIFSIZLT-UHFFFAOYSA-M sodium chloride Inorganic materials [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 34
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 27
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 22
- 239000011780 sodium chloride Substances 0.000 description 17
- 239000002244 precipitate Substances 0.000 description 16
- 239000000047 product Substances 0.000 description 13
- 238000006243 chemical reaction Methods 0.000 description 9
- 235000011121 sodium hydroxide Nutrition 0.000 description 9
- 238000003756 stirring Methods 0.000 description 9
- 230000007935 neutral effect Effects 0.000 description 8
- 238000002347 injection Methods 0.000 description 7
- 239000007924 injection Substances 0.000 description 7
- 239000000203 mixture Substances 0.000 description 7
- 238000011282 treatment Methods 0.000 description 7
- 239000000706 filtrate Substances 0.000 description 6
- 239000012535 impurity Substances 0.000 description 6
- 230000002378 acidificating effect Effects 0.000 description 5
- 239000007864 aqueous solution Substances 0.000 description 5
- 229910052751 metal Inorganic materials 0.000 description 5
- 239000002184 metal Substances 0.000 description 5
- 230000001225 therapeutic effect Effects 0.000 description 5
- IAJILQKETJEXLJ-KLVWXMOXSA-N (2s,3r,4r,5r)-2,3,4,5-tetrahydroxy-6-oxohexanoic acid Chemical compound O=C[C@H](O)[C@H](O)[C@@H](O)[C@H](O)C(O)=O IAJILQKETJEXLJ-KLVWXMOXSA-N 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- IAJILQKETJEXLJ-UHFFFAOYSA-N Galacturonsaeure Natural products O=CC(O)C(O)C(O)C(O)C(O)=O IAJILQKETJEXLJ-UHFFFAOYSA-N 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- 238000004061 bleaching Methods 0.000 description 4
- 239000013067 intermediate product Substances 0.000 description 4
- 230000035484 reaction time Effects 0.000 description 4
- 239000012465 retentate Substances 0.000 description 4
- MSWZFWKMSRAUBD-UHFFFAOYSA-N 2-Amino-2-Deoxy-Hexose Chemical compound NC1C(O)OC(CO)C(O)C1O MSWZFWKMSRAUBD-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical class [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- 241000282412 Homo Species 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- 229920002301 cellulose acetate Polymers 0.000 description 3
- 239000007795 chemical reaction product Substances 0.000 description 3
- 229910052802 copper Inorganic materials 0.000 description 3
- 239000010949 copper Chemical class 0.000 description 3
- 238000010612 desalination reaction Methods 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- -1 inorganic acids Chemical class 0.000 description 3
- 239000006228 supernatant Substances 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 229910052720 vanadium Chemical class 0.000 description 3
- LEONUFNNVUYDNQ-UHFFFAOYSA-N vanadium atom Chemical class [V] LEONUFNNVUYDNQ-UHFFFAOYSA-N 0.000 description 3
- KBPLFHHGFOOTCA-UHFFFAOYSA-N 1-Octanol Chemical compound CCCCCCCCO KBPLFHHGFOOTCA-UHFFFAOYSA-N 0.000 description 2
- 229920001287 Chondroitin sulfate Polymers 0.000 description 2
- OVBJJZOQPCKUOR-UHFFFAOYSA-L EDTA disodium salt dihydrate Chemical compound O.O.[Na+].[Na+].[O-]C(=O)C[NH+](CC([O-])=O)CC[NH+](CC([O-])=O)CC([O-])=O OVBJJZOQPCKUOR-UHFFFAOYSA-L 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 150000001447 alkali salts Chemical class 0.000 description 2
- 238000010923 batch production Methods 0.000 description 2
- 229920001429 chelating resin Polymers 0.000 description 2
- 239000003086 colorant Substances 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 150000002500 ions Chemical class 0.000 description 2
- 231100000636 lethal dose Toxicity 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 150000002739 metals Chemical class 0.000 description 2
- MGFYIUFZLHCRTH-UHFFFAOYSA-N nitrilotriacetic acid Chemical compound OC(=O)CN(CC(O)=O)CC(O)=O MGFYIUFZLHCRTH-UHFFFAOYSA-N 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 239000012466 permeate Substances 0.000 description 2
- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 229910052717 sulfur Inorganic materials 0.000 description 2
- 239000011593 sulfur Substances 0.000 description 2
- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 1
- KEQGZUUPPQEDPF-UHFFFAOYSA-N 1,3-dichloro-5,5-dimethylimidazolidine-2,4-dione Chemical compound CC1(C)N(Cl)C(=O)N(Cl)C1=O KEQGZUUPPQEDPF-UHFFFAOYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- HZZOUWBMMWVPTR-UHFFFAOYSA-N 2-[[6-[bis(carboxymethyl)amino]-1,4-dioxocan-6-yl]-(carboxymethyl)amino]acetic acid Chemical compound OC(=O)CN(CC(O)=O)C1(N(CC(O)=O)CC(O)=O)CCOCCOC1 HZZOUWBMMWVPTR-UHFFFAOYSA-N 0.000 description 1
- SQDAZGGFXASXDW-UHFFFAOYSA-N 5-bromo-2-(trifluoromethoxy)pyridine Chemical compound FC(F)(F)OC1=CC=C(Br)C=N1 SQDAZGGFXASXDW-UHFFFAOYSA-N 0.000 description 1
- FCKYPQBAHLOOJQ-UHFFFAOYSA-N Cyclohexane-1,2-diaminetetraacetic acid Chemical compound OC(=O)CN(CC(O)=O)C1CCCCC1N(CC(O)=O)CC(O)=O FCKYPQBAHLOOJQ-UHFFFAOYSA-N 0.000 description 1
- 229920002683 Glycosaminoglycan Polymers 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- QPCDCPDFJACHGM-UHFFFAOYSA-N N,N-bis{2-[bis(carboxymethyl)amino]ethyl}glycine Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(=O)O)CCN(CC(O)=O)CC(O)=O QPCDCPDFJACHGM-UHFFFAOYSA-N 0.000 description 1
- 239000004952 Polyamide Substances 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 206010047249 Venous thrombosis Diseases 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 239000002156 adsorbate Substances 0.000 description 1
- 150000007933 aliphatic carboxylic acids Chemical class 0.000 description 1
- 229910001854 alkali hydroxide Inorganic materials 0.000 description 1
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 1
- 230000002322 anti-exudative effect Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000002402 anti-lipaemic effect Effects 0.000 description 1
- 239000003146 anticoagulant agent Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 238000005341 cation exchange Methods 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 239000002738 chelating agent Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 229940068911 chloride hexahydrate Drugs 0.000 description 1
- XTHPWXDJESJLNJ-UHFFFAOYSA-N chlorosulfonic acid Substances OS(Cl)(=O)=O XTHPWXDJESJLNJ-UHFFFAOYSA-N 0.000 description 1
- 229940059329 chondroitin sulfate Drugs 0.000 description 1
- 238000004140 cleaning Methods 0.000 description 1
- ARUVKPQLZAKDPS-UHFFFAOYSA-L copper(II) sulfate Chemical compound [Cu+2].[O-][S+2]([O-])([O-])[O-] ARUVKPQLZAKDPS-UHFFFAOYSA-L 0.000 description 1
- 238000004042 decolorization Methods 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 230000008021 deposition Effects 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 238000005342 ion exchange Methods 0.000 description 1
- 239000003456 ion exchange resin Substances 0.000 description 1
- 229920003303 ion-exchange polymer Polymers 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- WPBNNNQJVZRUHP-UHFFFAOYSA-L manganese(2+);methyl n-[[2-(methoxycarbonylcarbamothioylamino)phenyl]carbamothioyl]carbamate;n-[2-(sulfidocarbothioylamino)ethyl]carbamodithioate Chemical compound [Mn+2].[S-]C(=S)NCCNC([S-])=S.COC(=O)NC(=S)NC1=CC=CC=C1NC(=S)NC(=O)OC WPBNNNQJVZRUHP-UHFFFAOYSA-L 0.000 description 1
- 230000000873 masking effect Effects 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 229910021645 metal ion Inorganic materials 0.000 description 1
- CXKWCBBOMKCUKX-UHFFFAOYSA-M methylene blue Chemical compound [Cl-].C1=CC(N(C)C)=CC2=[S+]C3=CC(N(C)C)=CC=C3N=C21 CXKWCBBOMKCUKX-UHFFFAOYSA-M 0.000 description 1
- 229960000907 methylthioninium chloride Drugs 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 238000010525 oxidative degradation reaction Methods 0.000 description 1
- 238000004806 packaging method and process Methods 0.000 description 1
- 229960003330 pentetic acid Drugs 0.000 description 1
- 150000004965 peroxy acids Chemical class 0.000 description 1
- 229920001467 poly(styrenesulfonates) Polymers 0.000 description 1
- 229920002492 poly(sulfone) Polymers 0.000 description 1
- 229920002647 polyamide Polymers 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 235000011056 potassium acetate Nutrition 0.000 description 1
- 239000001103 potassium chloride Substances 0.000 description 1
- 235000011164 potassium chloride Nutrition 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000009516 primary packaging Methods 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 238000004062 sedimentation Methods 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 235000015424 sodium Nutrition 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 230000019635 sulfation Effects 0.000 description 1
- 238000005670 sulfation reaction Methods 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 230000002537 thrombolytic effect Effects 0.000 description 1
- 230000002471 thromboprophylactic effect Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 238000005199 ultracentrifugation Methods 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08B—POLYSACCHARIDES; DERIVATIVES THEREOF
- C08B37/00—Preparation of polysaccharides not provided for in groups C08B1/00 - C08B35/00; Derivatives thereof
- C08B37/006—Heteroglycans, i.e. polysaccharides having more than one sugar residue in the main chain in either alternating or less regular sequence; Gellans; Succinoglycans; Arabinogalactans; Tragacanth or gum tragacanth or traganth from Astragalus; Gum Karaya from Sterculia urens; Gum Ghatti from Anogeissus latifolia; Derivatives thereof
- C08B37/0063—Glycosaminoglycans or mucopolysaccharides, e.g. keratan sulfate; Derivatives thereof, e.g. fucoidan
- C08B37/0069—Chondroitin-4-sulfate, i.e. chondroitin sulfate A; Dermatan sulfate, i.e. chondroitin sulfate B or beta-heparin; Chondroitin-6-sulfate, i.e. chondroitin sulfate C; Derivatives thereof
Priority Applications (19)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE3118588A DE3118588C2 (de) | 1981-05-11 | 1981-05-11 | Verfahren zur Herstellung eines injizierbaren hochreinen Chondroitinpolysulfates, hiernach erhältliches Produkt und pharmazeutische Zusammensetzung |
| US06/373,226 US4524066A (en) | 1981-05-11 | 1982-04-29 | Process for the preparation of injectable chondroitin polysulfate |
| BE0/208024A BE893097A (fr) | 1981-05-11 | 1982-05-06 | Procede de preparation d'un polysulfate de chondroitine injectable, produit obtenu par ce procede et compositions pharmaceutiques le contenant |
| NLAANVRAGE8201873,A NL186638C (nl) | 1981-05-11 | 1982-05-07 | Werkwijze voor het bereiden van een injecteerbaar chondroitine-polysulfaat, produkt verkrijgbaar met deze werkwijze alsmede een farmaceutisch preparaat. |
| CA000402613A CA1207758A (en) | 1981-05-11 | 1982-05-10 | Process for the preparation of an injectable chondroitin polysulfate, a product which can be obtained by this process and a pharmaceutical composition |
| JP57076774A JPS57192401A (en) | 1981-05-11 | 1982-05-10 | Injectable chondroitin polysulfate |
| AU83573/82A AU552545B2 (en) | 1981-05-11 | 1982-05-11 | Injectable chondroitin polysulphate |
| GB8213536A GB2098232B (en) | 1981-05-11 | 1982-05-11 | Injectable chondroitin polysulfate |
| CH2919/82A CH650788A5 (de) | 1981-05-11 | 1982-05-11 | Verfahren zur herstellung eines injizierbaren chondroitinpolysulfates, hiernach erhaeltliches produkt und dessen verwendung zur herstellung von pharmazeutischen zubereitungen. |
| DK211882A DK160317C (da) | 1981-05-11 | 1982-05-11 | Fremgangsmaade til fremstilling af et injicerbart chondroitinpolysulfat |
| IT21189/82A IT1157939B (it) | 1981-05-11 | 1982-05-11 | Processo per la preparazione di un polisolfato di condroitina iniettabile, un prodotto che puo' essere ottenuto con questo processo e una composizione farmaceutica |
| IE1127/82A IE53633B1 (en) | 1981-05-11 | 1982-05-11 | Process for the preparation of an injectable chondroitin polysulfate a product which can be obtained by this process and a pharmaceutical composition |
| SE8202947A SE458118B (sv) | 1981-05-11 | 1982-05-11 | Foerfarande foer framstaellning av ett injicerbart kondroitinpolysulfat, en produkt som kan erhaallas genom detta foerfarande och en farmaceutisk komposition |
| IL65743A IL65743A (en) | 1981-05-11 | 1982-05-11 | Injectable chondroitin polysulfate,its preparation and pharmaceutical compositions containing it |
| FR8208182A FR2505185B1 (fr) | 1981-05-11 | 1982-05-11 | Procede de preparation d'un polysulfate de chondroitine injectable, produit obtenu par ce procede et compositions pharmaceutiques le contenant |
| FI821651A FI70416C (fi) | 1981-05-11 | 1982-05-11 | Foerfarande foer framstaellning av en injektabel chondroitin polysulfat |
| LU84143A LU84143A1 (fr) | 1981-05-11 | 1982-05-11 | Procede de preparation d'un polysulfate de chondroitine injectable,produit obtenu par ce procede et compositions pharmaceutiques le contenant |
| AT0184282A AT387225B (de) | 1981-05-11 | 1982-05-11 | Verfahren zur herstellung eines injizierbaren chondroitinpolysulfates |
| NO821551A NO157147C (no) | 1981-05-11 | 1982-05-11 | Fremgangsmaate for fremstilling av et injiserbart chondroitin-polysulfat. |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE3118588A DE3118588C2 (de) | 1981-05-11 | 1981-05-11 | Verfahren zur Herstellung eines injizierbaren hochreinen Chondroitinpolysulfates, hiernach erhältliches Produkt und pharmazeutische Zusammensetzung |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DE3118588A1 DE3118588A1 (de) | 1982-12-02 |
| DE3118588C2 true DE3118588C2 (de) | 1983-07-07 |
Family
ID=6131969
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE3118588A Expired DE3118588C2 (de) | 1981-05-11 | 1981-05-11 | Verfahren zur Herstellung eines injizierbaren hochreinen Chondroitinpolysulfates, hiernach erhältliches Produkt und pharmazeutische Zusammensetzung |
Country Status (19)
| Country | Link |
|---|---|
| US (1) | US4524066A (es) |
| JP (1) | JPS57192401A (es) |
| AT (1) | AT387225B (es) |
| AU (1) | AU552545B2 (es) |
| BE (1) | BE893097A (es) |
| CA (1) | CA1207758A (es) |
| CH (1) | CH650788A5 (es) |
| DE (1) | DE3118588C2 (es) |
| DK (1) | DK160317C (es) |
| FI (1) | FI70416C (es) |
| FR (1) | FR2505185B1 (es) |
| GB (1) | GB2098232B (es) |
| IE (1) | IE53633B1 (es) |
| IL (1) | IL65743A (es) |
| IT (1) | IT1157939B (es) |
| LU (1) | LU84143A1 (es) |
| NL (1) | NL186638C (es) |
| NO (1) | NO157147C (es) |
| SE (1) | SE458118B (es) |
Families Citing this family (19)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3244214A1 (de) * | 1982-11-30 | 1984-05-30 | B. Braun Melsungen Ag, 3508 Melsungen | Verfahren zur reinigung und fraktionierung von heparin |
| US4623539A (en) * | 1983-02-04 | 1986-11-18 | Tunc Deger C | Nutrient barrier polysaccharide compositions and method of use |
| FR2572731B1 (fr) * | 1984-11-07 | 1987-03-06 | Sanofi Sa | Nouveaux sulfates de xylanes de bas poids moleculaires, leur procede de preparation et leur activite antithrombotique et hypolipemiante par voie orale |
| IT1214609B (it) * | 1985-05-17 | 1990-01-18 | Opocrin Spa | Esosaminoglicani solfati depolimerizzati ad attivita'antitrombotica, fibrinolitica, antinfiammatoria, loro procedimento di preparazione e composizioni farmaceutiche che li contengono. |
| US5145841A (en) * | 1987-03-19 | 1992-09-08 | Arthropharm Pty. Limited | Anti-inflammatory compounds and compositions |
| US5668116A (en) * | 1987-03-19 | 1997-09-16 | Anthropharm Pty. Limited | Anti-inflammatory compounds and compositions |
| DK0408770T3 (da) * | 1989-02-06 | 1996-10-07 | Taiho Pharmaceutical Co Ltd | Sulfateret polysaccharid, farmaceutisk acceptable salte heraf, fremstilling heraf og lægemiddel indeholdende samme som aktiv bestanddel |
| US5519010A (en) * | 1989-02-06 | 1996-05-21 | Taiho Pharmaceutical Co., Ltd. | Sulfated polysaccharide, pharmaceutically acceptable salt thereof, process for preparing same and medicament containing same as effective component |
| US5141928B1 (en) * | 1989-12-20 | 1995-11-14 | Brujo Inc | Ophthalmic medication |
| JPH05279381A (ja) * | 1991-09-13 | 1993-10-26 | Dainippon Ink & Chem Inc | 硫酸化オリゴ糖芳香族配糖体 |
| IT1256236B (it) * | 1992-12-23 | 1995-11-29 | Mediolanum Farmaceutici Srl | Oligosaccaridi aventi attivita' biologica e procedimento per la loro preparazione di glicosaminoglicani |
| IN181358B (es) * | 1995-02-14 | 1998-05-30 | Bioniche Inc | |
| US5880108A (en) * | 1995-02-14 | 1999-03-09 | Bioniche, Inc. | Method for treating the internal urinary bladder and associated structures using hyaluronic acid |
| US5591724A (en) * | 1995-02-14 | 1997-01-07 | Bioniche Inc. | Method for treating the urinary bladder and associated structures using hyaluronic acid |
| WO2000056298A2 (en) * | 1999-03-19 | 2000-09-28 | Luitpold Pharmaceuticals, Inc. | Treatment of lyme disease with polysulfated glycosaminoglycan formulations |
| EP1625135B1 (fr) * | 2003-02-27 | 2009-04-08 | Glaxo Group Limited | Composition de fondaparinux sodique de haute purete |
| JP4679138B2 (ja) * | 2004-12-24 | 2011-04-27 | 株式会社日本バリアフリー | 高純度化されたムコ多糖類の製造方法 |
| FR2969618B1 (fr) * | 2010-12-28 | 2014-05-16 | Pf Medicament | Procede de preparation de chondroitine sulfate de sodium |
| RU2677330C2 (ru) * | 2015-11-20 | 2019-01-16 | Закрытое Акционерное Общество "Фармфирма "Сотекс" | Способ приготовления инъекционной формы препарата хондроитина сульфата |
Family Cites Families (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE136572C (es) * | 1902-12-05 | |||
| DE870094C (de) * | 1950-10-17 | 1953-03-09 | Geigy Ag J R | Verfahren zur Herstellung von Polyschwefelsaeureestern des Chondroitins |
| DE935843C (de) * | 1951-07-12 | 1955-12-01 | Hoffmann La Roche | Verfahren zur Herstellung eines blutgerinnungshemmenden Mittels |
| US2767167A (en) * | 1953-07-06 | 1956-10-16 | Gen Mills Inc | Process of reducing the viscosity of gums |
| DE968752C (de) * | 1954-01-29 | 1958-03-27 | Hoffmann La Roche | Verfahren zur Herstellung von Chondroitinpolyschwefelsaeureestern |
| US2803558A (en) * | 1956-06-27 | 1957-08-20 | Commw Color & Chemical Co | Method of treating adhesive gums |
| US2959583A (en) * | 1959-01-23 | 1960-11-08 | Warner Lambert Pharmaceutical | Method of purifying sulfated polysaccharides |
| US3175942A (en) * | 1962-03-13 | 1965-03-30 | Evans Medical Ltd | Gastro-intestinal therapeutic |
| US3174904A (en) * | 1963-03-25 | 1965-03-23 | Rexall Drug Chemical | Method of purifying sulfated carbohydrates |
| US3405120A (en) * | 1966-01-27 | 1968-10-08 | Green Cross Corp | Low molecular chondroitin sulfate and method for manufacturing the same |
| US3454560A (en) * | 1966-03-01 | 1969-07-08 | Seikagaku Kogyo Co Ltd | Process for the production of chondroitin polysulfate |
| BE857389A (fr) * | 1977-08-02 | 1977-12-01 | Marbex Finance Ltd | Procede de preparation de chondroitines-sulfates de metaux alcalins et alcalino-terreux d'un poids moleculaire de 3000 a 6000 |
-
1981
- 1981-05-11 DE DE3118588A patent/DE3118588C2/de not_active Expired
-
1982
- 1982-04-29 US US06/373,226 patent/US4524066A/en not_active Expired - Lifetime
- 1982-05-06 BE BE0/208024A patent/BE893097A/fr not_active IP Right Cessation
- 1982-05-07 NL NLAANVRAGE8201873,A patent/NL186638C/xx not_active IP Right Cessation
- 1982-05-10 JP JP57076774A patent/JPS57192401A/ja active Granted
- 1982-05-10 CA CA000402613A patent/CA1207758A/en not_active Expired
- 1982-05-11 FI FI821651A patent/FI70416C/fi not_active IP Right Cessation
- 1982-05-11 NO NO821551A patent/NO157147C/no not_active IP Right Cessation
- 1982-05-11 LU LU84143A patent/LU84143A1/fr unknown
- 1982-05-11 FR FR8208182A patent/FR2505185B1/fr not_active Expired
- 1982-05-11 AU AU83573/82A patent/AU552545B2/en not_active Expired
- 1982-05-11 SE SE8202947A patent/SE458118B/sv not_active IP Right Cessation
- 1982-05-11 CH CH2919/82A patent/CH650788A5/de not_active IP Right Cessation
- 1982-05-11 IE IE1127/82A patent/IE53633B1/en not_active IP Right Cessation
- 1982-05-11 AT AT0184282A patent/AT387225B/de not_active IP Right Cessation
- 1982-05-11 IL IL65743A patent/IL65743A/xx not_active IP Right Cessation
- 1982-05-11 IT IT21189/82A patent/IT1157939B/it active Protection Beyond IP Right Term
- 1982-05-11 DK DK211882A patent/DK160317C/da not_active IP Right Cessation
- 1982-05-11 GB GB8213536A patent/GB2098232B/en not_active Expired
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| DE3118588C2 (de) | Verfahren zur Herstellung eines injizierbaren hochreinen Chondroitinpolysulfates, hiernach erhältliches Produkt und pharmazeutische Zusammensetzung | |
| DE4134854C2 (es) | ||
| DE3150318A1 (de) | "verfahren zur herstellung eines polysaccharidderivats des fibrinolysins" | |
| DE3519095A1 (de) | Verwendung von gm(pfeil abwaerts)1(pfeil abwaerts) oder eines davon abgeleiteten inneren esters zur therapie von gehirnschlaegen | |
| DE2417859C2 (de) | Verfahren zur Herstellung von einfachen oder gemischten Heparinsalzen und diese enthaltende Arzneimittel | |
| DE1618454A1 (de) | Neues Chondroitinsulfat und Verfahren zu seiner Herstellung | |
| DE2834702A1 (de) | Von mineralsalzen, insbesondere oxalaten, befreite heparinpraeparate, verfahren zu ihrer herstellung und ihre verwendung | |
| DE2734622C2 (es) | ||
| DE2725246C2 (es) | ||
| DE1443665A1 (de) | Komplex Eisen-hydriertes Dextran und Herstellungsverfahren hierfuer | |
| EP0537429B1 (de) | Modifizierte Huminate, Verfahren zu ihrer Herstellung und Verwendung | |
| DE2943167C2 (es) | ||
| DE1940130A1 (de) | Injizierbare Insulinaufbereitungen fuer klinische Zwecke und Verfahren zu ihrer Herstellung | |
| DE938502C (de) | Verfahren zur Herstellung einer kolloidalen Eisenzubereitung | |
| DE1493618A1 (de) | Cumarinderivate und ein Verfahren zu ihrer Herstellung | |
| DE2131153A1 (de) | Wasserloesliche antibakterielle Verbindungen unterirdischer Stollen | |
| DE945407C (de) | Verfahren zur Gewinnung und Reindarstellung von Bacitracin | |
| DE1492155C (de) | Verfahren zur Extraktion von Hydroxy flavan 3,4 diolen | |
| DE1811054C (de) | alpha hoch 5-0-Acylpyridoxale und Verfahren zu ihrer Herstellung | |
| DE69910424T2 (de) | Methode zur herstellung eines wirkstoffes zur behandlung von ulcera des organismus | |
| DE1617930C (de) | Verfahren zur Reinigung roher Präparate des Proteasen-Inhibitors aus Rinderlunge | |
| DE2544183A1 (de) | Verfahren zur herstellung eines biologisch aktiven mucoprotids | |
| DE1242202B (de) | Verfahren zur Herstellung von antilipaemisch wirksamen Alkalisalzen von Dextranschwefelsaeureestern | |
| DE1057287B (de) | Verfahren zur Herstellung reiner, therapeutisch verwendbarer Heparinpraeparate | |
| DEA0022737MA (es) |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| 8110 | Request for examination paragraph 44 | ||
| D2 | Grant after examination | ||
| 8364 | No opposition during term of opposition | ||
| 8327 | Change in the person/name/address of the patent owner |
Owner name: LUITPOLD PHARMA GMBH, 8000 MUENCHEN, DE |
|
| 8327 | Change in the person/name/address of the patent owner |
Owner name: LUITPOLD PHARMACEUTICALS, INC., SHIRLEY, N.Y., US |
|
| 8328 | Change in the person/name/address of the agent |
Free format text: ZUMSTEIN & KLINGSEISEN, 80331 MUENCHEN |